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Update on mangement of patent ductus arteriosus in preterm infants Dr..  Early, severe pulmonary hemorrhage is associated with ductal patency at 12 to 18 hours first week is not relate

Update on mangement of patent ductus arteriosus in

preterm infants

Dr Trinh Thi Thu Ha

1 Overview of PDA

2 Timing of screening PDA?

3 When to treat PDA?

Timing of ductal

closure

Prenatal MgSO4, tocolytic Postnatal surfactant

 Early, severe pulmonary hemorrhage is

associated with ductal patency at 12 to 18 hours

first week) is not related to persistent ductal

patency

(Workbook in Practical Neonatology 5th Edition 2015)

 Diagnosis: In most cases, the clinically silent

PDA during the first few days goes undetected unless an echocardiogram is performed

 Signs of bounding pulses, active precordium, and

systolic murmur were of reasonable specificity but

for diagnosis of an echocardiographically defined significant PDA

 Relying on clinical signs alone led to a mean

diagnostic delay of 2 days

(A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for patent ductus arteriosus Skelton R 1 , Evans N , Smythe J.

JPaediatr Child Health 1994 Oct;30(5):406-11)

Timing of screening PDA?

• Objective: To evaluate the association between

early screening echocardiography for PDA and in-hospital mortality

• Exposures: Early screening echocardiography

before day 3 of life.

• Design, Setting, and Participants:

 National prospective population-based cohort

 All preterms <=29 weeks hospitalized in 68 NICU

in France from April through December 2011.

• Main Outcomes and Measures:

Death between day 3 and discharge

Neonatal morbidities (pulmonary

hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis)

 Treat for PDA more frequently (55.1% vs 43.1%; [OR], 1.62 [95% CI, 1.31 to 2.00]

 Lower in-hospital mortality (55.1% vs 43.1%;

OR, 0.73 [95% CI, 0.54 to 0.98])

 Lower risk of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 [95% CI, 0.38 to 0.95]

 No different in severe BPD, severe cerebral

lesions, and NEC

Result

1210 preterm infants

 Options for dealing with PDA in preterm infants :

(1) Prophylactic pharmacologictreatment (COX

Prophylactic Pharmacotherapy ?

Administering COX inhibitors (indomethacin or

ibuprofen) within the first 24h of life irrespective of the diagnosis of PDA

Indomethacin is the best studied with 2872 babies randomised in 19 trials

Indomethacin Prophylaxis

 Some clinicians recommend indomethacin prophylaxis for extremely immature babies (23–25 weeks) to prevent IVH

 At this time, less than 30% of neonatologists in the United States use indomethacin “prophylactically”, despite its short- term benefits

(Jhaveri N, Soll RF, Clyman RI Feeding practices and patent ductus arteriosus ligation preferences-are they related? Am J Perinatol 2009;27:667–674 [ PubMed ])

Ibuprofen Prophylaxis

 No significant differences in mortality, IVH, or BPD

 No reduction in IVH, PAL in the treated group

 Increased risk of gastrointestinal bleeding

 Prophylactic ibuprofen exposes many infants to renal and gastrointestinal side effects without any important short-term benefits and is not recommended

Pre-symptomatic Pharmacologic Treatment

 No effect on the rate of

mortality, BPD, IVH, ROP,

or length of ventilation,

death, IVH, NEC,…

 More renal side effect

 Presymptomatic

indomethacin or ibuprofen

therapy for PDA in preterm

infants is not recommended.

Conservative Management

 Fluid restriction

 Diuretics, avoidance of loop diuretics

 Maintaining a hematocrit of 35 to 40 percent

 Increased positive airway pressure

 Correction of alkalosis

 Avoidance of pulmonary vasodilators: oxygen or NO

 Asymptomatic infants with PDAs generally do not require medical management or surgical ligation These infants should be monitored for evidence of CHF, failure or renal impairment, increasing oxygen requirement, or other

complications

Pharmacological closure

• Indomethacine

• Ibuprofen

• Paracetamol (?)

33 studies, 2190 infants, iv and oral administration

Paracetamol ?

 Paracetamol act at the

peroxidase segment of the

enzyme

 Peroxidase activated at lower peroxide concentrations

10-fold-than is cyclooxygenase

 Firstline therapy, used when

ibuprofen was contraindicated, and as rescue therapy, used when ibuprofen failed

( PubMed Paracetamol for the treatment of patent ductus arteriosus in preterm neonates:

a systematic review and meta-analysis)

 Some clinicians allow trophic feeds or

continue the current feeding volume but do not advance the feeding regimen during

treatment (NICU Primer for Pharmacists)

Surgical ligation

 If the patient remains symptomatic after one or

two courses of cyclooxygenase (COX) inhibitor

or if COX inhibitor treatment is contraindicated

 Risks of blood pressure fluctuations,

respiratory compromise, infection,

intraventricular hemorrhage (IVH),chylothorax, recurrent laryngeal nerve paralysis.

Percutaneous transcatheter

occlusion

1) Outcomes of transcatheter occlusion of patent ductus

arteriosus in infants weighing ≤ 6 kg JACC Cardiovasc

Interv 2010; 3:1295.

2) Percutaneous Patent Ductus Arteriosus (PDA) Closure in

Very Preterm Infants: Feasibility and Complications J Am Heart Assoc 2016; 5

3) Transcatheter occlusion of patent ductus arteriosus in

pre­term infants JACC Cardiovasc Interv 2010; 3:550.

both efficacy and safety

 No randomized controlled trials comparing long-term outcomes of the three different

approaches no data to determine the

optimal management of PDA in preterm

infants  Practice can vary from NICU to

NICU

 Relying on clinical signs alone led to a mean diagnostic delay of 2 days

 Early screening echocardiography before day 3 of life

 Severe pulmonary hemorrhage is

associated with ductal patency at 12 to 18

hours of age, but later pulmonary

hemorrhage (after the first week) is not

related to persistent ductal patency

 Infants 23-25 wk (without antenatal steroid)

at a higher risk of PDA-related morbidities and would benefit from prophylactic low-

dose indomethacin for prevention of IVH

Presymptomatic indomethacin or ibuprofen therapy for PDA in preterm infants is not

recommended

Ibuprofen is equally effective but has fewer adverse effects

Paracetamol can be used when ibuprofen was contraindicated

 Continue the current feeding volume but

do not advance the feeding regimen

during treatment

 Avoidance of loop diuretics

Thank you